Antagonists to IL-6 to Raise Albumin and/or Lower CRP
The present invention is directed to therapeutic methods using IL-6 antagonists such as antibodies and fragments thereof having binding specificity for IL-6 to improve survivability or quality of life of a patient in need thereof. In preferred embodiments these patients will comprise those exhibiting (or at risk of developing) an elevated serum C-reactive protein level or a reduced serum albumin level prior to treatment. In another preferred embodiment, the patient's Glasgow Prognostic Score will be increased and survivability will preferably be improved.
1 - 81 . (canceled)
82 . A method of improving survivability or quality of life of a patient in need thereof, comprising administering to the patient an IL-6 antagonist, whereby the patient's serum C-reactive protein (“CRP”) level is reduced, and optionally monitoring the patient to assess the reduction in the patient's serum CRP level, wherein the anti-IL-6 antibody or antibody fragment comprises the same CDRs as an anti-IL-6 antibody selected from the group consisting of Ab1, Ab2, Ab3, Ab4, Ab5, Ab6, Ab7, Ab8, Ab9, Ab10, Ab11, Ab12, Ab13, Ab14, Ab15, Ab16, Ab17, Ab18, Ab19, Ab20, Ab21, Ab22, Ab23, Ab24, Ab25, Ab26, Ab27, Ab28, Ab29, Ab30, Ab31, Ab32, Ab33, Ab34, Ab35, and Ab36.
83 . A method of improving survivability or quality of life of a patient in need thereof, comprising administering to the patient an IL-6 antagonist, whereby the patient's serum albumin level is increased, and optionally monitoring the patient to assess the increase in the patient's serum albumin level wherein the anti-IL-6 antibody or antibody fragment comprises the same CDRs as an anti-IL-6 antibody selected from the group consisting of an anti-IL-6 antibody selected from the group consisting of Ab1, Ab2, Ab3, Ab4, Ab5, Ab6, Ab7, Ab8, Ab9, Ab10, Ab11, Ab12, Ab13, Ab14, Ab15, Ab16, Ab17, Ab18, Ab19, Ab20, Ab21, Ab22, Ab23, Ab24, Ab25, Ab26, Ab27, Ab28, Ab29, Ab30, Ab31, Ab32, Ab33, Ab34, Ab35, and Ab36.
84 . A method of improving survivability or quality of life of a patient in need thereof, comprising administering to the patient an IL-6 antagonist, whereby the patient's serum CRP level is reduced and the patient's serum albumin level is increased, and optionally monitoring the patient to assess the reduction in the patient's serum CRP level and the increase in the patient's serum albumin level, wherein the anti-IL-6 antibody or antibody fragment wherein the anti-IL-6 antibody or antibody fragment comprises the same CDRs as an anti-IL-6 antibody selected from the group consisting of an anti-IL-6 antibody selected from the group consisting of Ab1, Ab2, Ab3, Ab4, Ab5, Ab6, Ab7, Ab8, Ab9, Ab10, Ab11, Ab12, Ab13, Ab14, Ab15, Ab16, Ab17, Ab18, Ab19, Ab20, Ab21, Ab22, Ab23, Ab24, Ab25, Ab26, Ab27, Ab28, Ab29, Ab30, Ab31, Ab32, Ab33, Ab34, Ab35, and Ab36.
85 . The method of claim 82 , wherein the patient has asthma.
86 . The method of claim 83 , wherein the patient has asthma.
87 . The method of claim 84 , wherein the patient has asthma.
88 . The method of claim 82 , wherein said patient has an elevated serum CRP level prior to treatment.
89 . The method of claim 84 , wherein said patient has an elevated serum CRP level prior to treatment.
90 . The method of claim 83 , wherein said patient has a decreased serum albumin level prior to treatment.
91 . The method of claim 84 , wherein said patient has a decreased serum albumin level prior to treatment.
92 . A method of improving survivability or quality of life of a patient diagnosed with a disease associated with increased CRP, said disease selected from psoriasis, psoriatic arthropathy, ankylosing spondylitis, systemic lupus erythematosus, Crohn's disease, ulcerative colitis, pemphigus, dermatomyositis, polymyositis, polymyalgia rheumatica, giant cell arteritis, vasculitis, polyarteritis nodosa, Wegener's granulomatosis, Kawasaki disease, isolated CNS vasculitis, Churg-Strauss arteritis, microscopic polyarteritis, microscopic polyangiitis, Henoch-Schönlein purpura, essential cryoglobulinemic vasculitis, rheumatoid vasculitis, cryoglobulinemia, relapsing polychondritis, Behçet's disease, Takayasu's arteritis, ischemic heart disease, stroke, multiple sclerosis, sepsis, vasculitis secondary to viral infection, Buerger's Disease, cancer, advanced cancer, Osteoarthritis, systemic sclerosis, CREST syndrome, Reiter's disease, Paget's disease of bone, Sjögren's syndrome, diabetes type 1, diabetes type 2, familial Mediterranean fever, autoimmune thrombocytopenia, autoimmune hemolytic anemia, autoimmune thyroid diseases, pernicious anemia, vitiligo, alopecia greata, primary biliary cirrhosis, autoimmune chronic active hepatitis, alcoholic cirrhosis, viral hepatitis, burns, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, allergic asthma, or any combination thereof, by decreasing the patient's serum C reactive protein (“CRP”) level, comprising administering to the patient an effective amount of an anti-IL-6 antibody or antibody fragment that blocks the binding of human IL-6 to IL-6R1 and the binding of IL-6 to gp130, whereby the patient's CRP-level is reduced, and the patient's serum C reactive protein (“CRP”) level is reduced, wherein the anti-IL-6 antibody or antibody fragment comprises a V L polypeptide comprising CDR1, CDR2 and CDR3 polypeptides respectively having the amino acid sequences of SEQ ID NO:4, 5 and 6 and a V H polypeptide comprising CDR1, CDR2 and CDR3 polypeptides respectively having the amino acid sequences of SEQ ID NO:7, 8 or 120, and 9.
93 . A method of improving survivability or quality of life of a patient diagnosed with a disease associated with increased CRP and/or decreased serum albumin, said disease selected from psoriasis, psoriatic arthropathy, ankylosing spondylitis, systemic lupus erythematosus, Crohn's disease, ulcerative colitis, pemphigus, dermatomyositis, polymyositis, polymyalgia rheumatica, giant cell arteritis, vasculitis, polyarteritis nodosa, Wegener's granulomatosis, Kawasaki disease, isolated CNS vasculitis, Churg-Strauss arteritis, microscopic polyarteritis, microscopic polyangiitis, Henoch-Schonlein purpura, essential cryoglobulinemic vasculitis, rheumatoid vasculitis, cryoglobulinemia, relapsing polychondritis, Behçet's disease, Takayasu's arteritis, ischemic heart disease, stroke, multiple sclerosis, sepsis, vasculitis secondary to viral infection, Buerger's Disease, cancer, advanced cancer, Osteoarthritis, systemic sclerosis, CREST syndrome, Reiter's disease, Paget's disease of bone, Sjögren's syndrome, diabetes type 1, diabetes type 2, familial Mediterranean fever, autoimmune thrombocytopenia, autoimmune hemolytic anemia, autoimmune thyroid diseases, pernicious anemia, vitiligo, alopecia greata, primary biliary cirrhosis, autoimmune chronic active hepatitis, alcoholic cirrhosis, viral hepatitis, burns, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, allergic asthma, or any combination thereof, by decreasing the patient's serum C reactive protein (“CRP”) levels and/or by increasing serum albumin levels, comprising administering to the patient an effective amount of an anti-IL-6 antibody or antibody fragment that blocks the binding of human IL-6 to IL-6R1, and the binding of IL-6 to gp130, whereby the patient's serum albumin levels are increased and/or the patient's serum C reactive protein (“CRP) levels are reduced, wherein the anti-IL-6 antibody or antibody fragment comprises a V L polypeptide comprising CDR1, CDR2 and CDR3 polypeptides respectively having the amino acid sequences of SEQ ID NO:4, 5 and 6 and a V H polypeptide comprising CDR1, CDR2 and CDR3 polypeptides respectively having the amino acid sequences of SEQ ID NO:7, 8 or 120, and 9.
94 . The method of claim 92 , wherein the anti-IL-6 antibody or fragment comprises the variable heavy and light chain amino acid sequences of SEQ ID NO: 657 and 709, respectively.
95 . The method of claim 93 , wherein the anti-IL-6 antibody or fragment comprises the variable heavy and light chain amino acid sequences of SEQ ID NO: 657 and 709, respectively.
96 . The method of claim 94 , wherein the anti-IL-6 antibody or fragment comprises the variable heavy and light chain amino acid sequences of SEQ ID NO: 657 and 709, respectively.
97 . The method of claim 94 , wherein the anti-IL-6 antibody or fragment comprises the variable heavy and light chain polypeptides comprising the amino acid sequences of SEQ ID NO: 657 and 709 respectively, and further comprises the heavy chain and light chain constant regions comprising the amino acid sequences of SEQ ID NO: 588 and SEQ ID NO: 586 respectively.
98 . The method of claim 95 , wherein the anti-IL-6 antibody or fragment comprises the variable heavy and light chain polypeptides comprising the amino acid sequences of SEQ ID NO: 657 and 709 respectively, and further comprises the heavy chain and light chain constant regions comprising the amino acid sequences of SEQ ID NO: 588 and SEQ ID NO: 586 respectively.
99 . The method of claim 96 , wherein the anti-IL-6 antibody or fragment comprises the variable heavy and light chain polypeptides comprising the amino acid sequences of SEQ ID NO: 657 and 709 respectively, and further comprises the heavy chain and light chain constant regions comprising the amino acid sequences of SEQ ID NO: 588 and SEQ ID NO: 586 respectively.